Sensors for measuring parameters in a test fluid are widely used in various fields of chemistry, biology and physiology.
In order to assure that sensor measurements are accurate, the sensor should be regularly calibrated. Calibrating the sensor typically involves determining experimentally the correspondence between a sensor response and a predetermined parameter value of a reference material, and adjusting the sensor in accordance therewith.
The quality of the sensor performance should also be controlled on a regular basis to verify experimentally that the sensor measurements are accurate. This is usually done by comparing a measured parameter value of a reference material to an acceptance range of the same reference material.
Reference materials for calibration and quality control routines comprise compounds, which represent the parameter in question. The parameter may be a physical parameter, such as viscosity, density, pressure and conductivity, or a chemical parameter, such as pH or the concentration of gasses, electrolytes or metabolites of a physiological liquid, like blood. The reference materials should represent the parameter precisely and steadily over their lifetime. Therefore, reference materials may comprise compounds in concentrations which are stable over time, e.g., compounds in chemical equilibrium, and they should be prepared and stored under closely controlled conditions to assure fulfillment of their specifications.
In some cases such controlled conditions of preparation and storage may not suffice to fulfill the specifications. This may be the case with a reference solution comprising two compounds which exist in equilibrium and which are mutually convertible into each other. The equilibrium between such two compounds may be temperature dependent. If so, then, any temperature change is likely to gradually change the chemical composition of the reference solution.
One such reference solution may include a dissolved gas, in which the gas may be distributed between a gaseous phase in a container headspace and a dissolved phase in the solution. With such a system, the equilibrium distribution of gas between the two phases may be temperature dependent. Thus, if the solution is stored at a temperature different from the operating temperature, the distribution of gas may be different from the equilibrium distribution at the operating temperature. The reference solution may therefore need long term conditioning before use in order to establish a state of equilibrium between the two phases corresponding to the operating temperature.
Another type of two-phase reference solution is a system comprising a sparingly soluble compound, which may exist partly as solute and partly as solid phase. The distribution between these two phases may be temperature dependent, and the solution may also need long term conditioning before use in order to establish a state of equilibrium at the operating temperature.
Still other reference solutions involve chemical reactions, in which two or more compounds exist in equilibrium. Examples include the systems of glutamine and glutamic acid/glutamate and of carbon dioxide and carbonic acid, as well as the mutarotational system of α-D-glucose and β-D-glucose. Reference solutions comprising these compounds may require conditioning for days, months or even years before use in order to establish a state of equilibrium at the operating temperature.
Yet another example of a system comprising two compounds in equilibrium is the system of creatinine and creatine. As with the examples above, long term conditioning may be needed as the equilibrium between these two compounds is established only over a period of months or years.
International Published Patent Application WO 02/14533 to Roche Diagnostics GmbH discloses a method of calibrating a creatinine sensor. According to this method, two calibration solutions are used. The first calibration solution is an acidic solution of creatinine, which is first neutralized before being used for calibration. The neutralization step, however, makes this procedure inconvenient for daily operation. The second solution is a solution of creatinine and creatine at equilibrium concentrations corresponding to a specific temperature. However, to avoid compositional changes, such a solution should either be prepared immediately before use or kept at that specific temperature, both of which are impractical in daily use.
Thus, despite the hitherto proposed reference solutions for detection of mutually convertible compounds, there is still a need for a reference solution which does not require extended conditioning and/or instant preparation. Accordingly, it is an object of the present invention to provide such a reference solution.